Asunto(s)
Humanos , Masculino , Femenino , Anciano , Anciano de 80 o más Años , Claritromicina/efectos adversos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Inhibidores del Citocromo P-450 CYP3A/efectos adversos , Pirimidinas/metabolismo , Pirimidinas/uso terapéutico , Pirimidinas/farmacocinética , Rabdomiólisis/inducido químicamente , Sulfonamidas/metabolismo , Sulfonamidas/uso terapéutico , Sulfonamidas/farmacocinética , Ácidos Grasos Monoinsaturados/metabolismo , Ácidos Grasos Monoinsaturados/uso terapéutico , Ácidos Grasos Monoinsaturados/farmacocinética , Pravastatina/metabolismo , Pravastatina/uso terapéutico , Pravastatina/farmacocinética , Inhibidores de Hidroximetilglutaril-CoA Reductasas/metabolismo , Transportadores de Anión Orgánico , Transportadores de Anión Orgánico Sodio-Independiente/antagonistas & inhibidores , Transportador 1 de Anión Orgánico Específico del Hígado , Interacciones Farmacológicas , Lesión Renal Aguda/inducido químicamente , Rosuvastatina Cálcica , Fluorobencenos/metabolismo , Fluorobencenos/uso terapéutico , Fluorobencenos/farmacocinética , Miembro 1B3 de la Familia de los Transportadores de Solutos de Aniones Orgánicos , Fluvastatina , Hiperpotasemia/inducido químicamente , Indoles/metabolismo , Indoles/uso terapéutico , Indoles/farmacocinéticaRESUMEN
The aim of this study is to evaluate the efficacy of total saponins of Dioscorea (TSD), an extract of the Chinese herbal Bi Xie, on hyperuricemia and to elucidate the underlying mechanisms. The rat hyperuricemia model was established by administration of adenine. Thirty-two rats were randomly allocated into 4 groups: model group, low/high-dose TSD-treated groups, and allopurinol-treated group. Meanwhile, 8 rats were used as normal controls. Serum uric acid (UA), blood urea nitrogen (BUN), serum creatinine (Scr), and organic anion transporting polypeptide 1A1 (OATP1A1) levels were measured. Comparison between the model group and treatment (allopurinol and TSD) groups showed the serum UA levels were significantly decreased in treatment groups. TSD had similar effects to allopurinol. It was found that the OATP1A1 protein expression levels in treatment groups were higher than in model group and normal controls. And different from the allopurinol-treated groups, TSD-treated group had elevated OATP1A1 expression levels in the stomach, liver, small intestine and large intestine tissues. It was suggested that TSD may facilitate the excretion of UA and lower UA levels by up-regulating OATP1A1 expression.
Asunto(s)
Animales , Masculino , Ratas , Creatinina , Sangre , Dioscorea , Química , Medicamentos Herbarios Chinos , Farmacología , Usos Terapéuticos , Hiperuricemia , Quimioterapia , Intestinos , Metabolismo , Hígado , Metabolismo , Transportadores de Anión Orgánico Sodio-Independiente , Genética , Metabolismo , Ratas Sprague-Dawley , Saponinas , Farmacología , Usos Terapéuticos , Estómago , Metabolismo , Regulación hacia Arriba , Ácido Úrico , SangreRESUMEN
<p><b>OBJECTIVE</b>To study the effect of Zhusha Anshen pill, cinnabar, HgS, HgCl2 and MeHg on the gene expression of renal transporters in mice.</p><p><b>METHOD</b>Healthy male mice were given equivalent physiological saline, Zhusha Anshen pill (1.8 g · kg(-1), containing 0.17 g · kg(-1) of mercury), cinnabar (0.2 g · kg(-1), containing 1.7 g · kg(-1) of mercury), high dose cinnabar (2 g · kg(-1), containing 1.7 g · kg(-1) of mercury), HgS (0.2 g · kg(-1), containing 0.17 g · kg(-1) of mercury), HgCl2 (0.032 g · kg(-1), containing 0. 024 g · kg(-1) of mercury), MeHg (0.026 g · kg(-1), containing 0.024 g · kg(-1) of mercury), once daily, for 30 d, measuring body mass gain. 30 days later, the mice were sacrificed. The mercury accumulation in kidneys was detected with atomic fluorescence spectrometer. Expressions of Oat1, Oat2, Oat3, Mrp2, Mrp4, Urat1 were detected with RT-PCR.</p><p><b>RESULT</b>Compared with the normal control group, a significant accumulation of Hg in kidney in HgCl2 and MeHg groups was observed (P <0.05), but these changes were not found in other groups. Compared with normal control group, mRNA expressions of Oat1 and Oat2 were evidently lower in HgCl2 and MeHg groups, but mRNA expressions of Mrp2 were apparently higher in HgCl2 group (P <0.05), mRNA expression of Mrp4 was significant higher in HgCl2 and MeHg groups, and mRNA expression of Urat1 was apparently lower in MeHg group.</p><p><b>CONCLUSION</b>HgCl2 and MeHg groups show significant difference from the normal group in mercury accumulation in kidneys and gene expression of kidney transporters, but with no difference between other groups and the normal group. Compared with HgCl2 and MeHg, cinnabar and its compounds could cause lower renal toxicity to mice.</p>
Asunto(s)
Animales , Masculino , Ratones , Proteínas Portadoras , Genética , Medicamentos Herbarios Chinos , Toxicidad , Expresión Génica , Riñón , Metabolismo , Cloruro de Mercurio , Toxicidad , Compuestos de Mercurio , Toxicidad , Compuestos de Metilmercurio , Toxicidad , Proteínas Asociadas a Resistencia a Múltiples Medicamentos , Genética , Proteína 1 de Transporte de Anión Orgánico , Genética , Transportadores de Anión Orgánico Sodio-Independiente , GenéticaRESUMEN
Liver is regarded as one of the most important organs for drug clearance in the body, which mediates both the metabolism and biliary excretion of drugs. Transporters are a class of functional membrane proteins and control the movement of substances into or out of cells. Transporters, which are extensively expressed in the liver, play important roles in the drug hepatic disposition by regulating the uptake of drugs from blood into hepatocytes or the efflux of drugs and their metabolites into bile. In this review, the localization, functions and substrate selectivity of the major transporters in the liver will be summarized, and the impacts of these transporters on drug hepatic disposition, the potential drug-drug interactions as well as their genetic polymorphisms will also be reviewed.
Asunto(s)
Humanos , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2 , Transportadoras de Casetes de Unión a ATP , Genética , Metabolismo , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP , Genética , Metabolismo , Bilis , Metabolismo , Transporte Biológico , Interacciones Farmacológicas , Hígado , Metabolismo , Proteínas de Transporte de Membrana , Genética , Metabolismo , Tasa de Depuración Metabólica , Proteínas Asociadas a Resistencia a Múltiples Medicamentos , Genética , Metabolismo , Proteínas de Neoplasias , Genética , Metabolismo , Transportadores de Anión Orgánico , Genética , Metabolismo , Transportadores de Anión Orgánico Sodio-Dependiente , Metabolismo , Transportadores de Anión Orgánico Sodio-Independiente , Genética , Metabolismo , Proteínas de Transporte de Catión Orgánico , Genética , Metabolismo , Farmacocinética , Polimorfismo Genético , Simportadores , MetabolismoRESUMEN
This paper reports on issues relating to the optimal use of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid magnetic resonance imaging (Gd-EOB-DTPA MR imaging) together with the generation of consensus statements from a working group meeting, which was held in Seoul, Korea (2010). Gd-EOB-DTPA has been shown to improve the detection and characterization of liver lesions, and the information provided by the hepatobiliary phase is proving particularly useful in differential diagnoses and in the characterization of small lesions (around 1-1.5 cm). Discussion also focused on advances in the role of organic anion-transporting polypeptide 8 (OATP8) transporters. Gd-EOB-DTPA is also emerging as a promising tool for functional analysis, enabling the calculation of post-surgical liver function in the remaining segments. Updates to current algorithms were also discussed.
Asunto(s)
Humanos , Algoritmos , Medios de Contraste , Diagnóstico Diferencial , Gadolinio DTPA , Hepatopatías/diagnóstico , Pruebas de Función Hepática , Imagen por Resonancia Magnética , Transportadores de Anión Orgánico Sodio-Independiente/metabolismo , Complicaciones Posoperatorias/diagnóstico , Guías de Práctica Clínica como AsuntoRESUMEN
OATP1B3, a member of SLC superfamily, is specifically expressed on the sinusoidal membrane of hepatocytes and is considered to be important in hepatic drug elimination. The overexpression of OATP1B3 was found recently in tumor tissues such as prostate, colon, and pancreatic tumors. Sequence variations in SLCO1B3 gene, such as SNPs, have been described and a common haplotype consisting of 334T>G and 699G>A SNPs is related to altered transport characteristics of OATP1B3. OATP1B3 is of relevance to drug metabolism through affecting alteration of hepatic concentration of endo- and xenobiotic compounds that interact with nuclear receptors such as PXR and CAR, and thereby directly alter the extent of target gene transcription, including major CYP isoenzymes such as CYP3A4. This review will provide an overview of substrates and inhibitors of OATP1B3 and subsequently to assess the effect of genetic mutation on transport activity. The studies linking OATP1B3 with cancer clinical outcomes are also discussed in this review.